The effect of fluid bolus administration on cerebral tissue oxygenation in post-cardiac arrest patients.

PURPOSE: Fluid boluses (FB) are often used in post-cardiac arrest (CA) patients with haemodynamic instability. Although FB may improve cardiac output (CO) and mean arterial pressure (MAP), FB may also increase central venous pressure (CVP), reduce arterial PaO2, dilute haemoglobin and cause interstitial oedema. The aim of the present study was to investigate the net effect of FB administration on cerebral tissue oxygenation saturation (SctO2) in post-CA patients. METHODS: Pre-planned sub-study of the Neuroprotect post-CA trial (NCT02541591). Patients with anticipated fluid responsiveness based on stroke volume variation (SVV) or passive leg raising test were administered a FB of 500 ml plasma-lyte A (Baxter Healthcare) and underwent pre- and post-FB assessments of stroke volume, CO, MAP, CVP, haemoglobin, PaO2 and SctO2. RESULTS: 52 patients (mean age 64 ±â€¯12 years, 75% male) received a total of 115 FB. Although administration of a FB resulted in a significant increase of stroke volume (63 ±â€¯22 vs 67 ±â€¯23 mL, p = 0.001), CO (4,2 ±â€¯1,6 vs 4,4 ±â€¯1,7 L/min, p = 0.001) and MAP (74,8 ±â€¯13,2 vs 79,2 ±â€¯12,9 mmHg, p = 0.004), it did not improve SctO2 (68.54 ±â€¯6.99 vs 68.70 ±â€¯6.80%, p = 0.49). Fluid bolus administration also resulted in a significant increase of CVP (10,0 ±â€¯4,5 vs 10,7 ±â€¯4,9 mmHg, p = 0.02), but did not affect PaO2 (99 ±â€¯31 vs 94 ±â€¯31 mmHg, p = 0.15) or haemoglobin concentrations (12,9 ±â€¯2,1 vs 12,8 ±â€¯2,2 g/dL, p = 0.10). In a multivariate model, FB-induced changes in CO (beta 0,77; p = 0.004) and in CVP (beta -0,23; p = 0.02) but not in MAP (beta 0,02; p = 0.18) predicted post-FB ΔSctO2. CONCLUSIONS: Despite improvements in CO and MAP, FB administration did not improve SctO2 in post-cardiac arrest patients.

The impact of global hemodynamics, oxygen and carbon dioxide on epileptiform EEG activity in comatose survivors of out-of-hospital cardiac arrest.

AIM: To study the association between global hemodynamics, blood gases, epileptiform EEG activity and survival after out-of-hospital CA (0HCA). METHODS: We retrospectively analyzed 195 comatose post-CA patients. At least one EEG recording per patient was evaluated to diagnose epileptiform EEG activity. Refractory epileptiform EEG activity was defined as persisting epileptic activity on EEG despite the use of 2 or more anti-epileptics. The time weighted average mean arterial pressure 48h (TWA-MAP48), the percentage of time with a MAP below 65 and above 85mmHg and the percentage of time with normoxia, hypoxia (<70mmHg), hyperoxia (>150mmHg), normocapnia, hypocapnia (<35mmHg) and hypercapnia (>45mmHg) were calculated. RESULTS: We observed epileptiform EEG activity in 57 patients (29%). A shockable rhythm was associated with a decreased likelihood of epileptic activity on the EEG (OR: 0.41, 95%CI 0.22-0.79). We did not identify an association between the TWA-MAP48, the percentage of time with MAP below 65mmHg or above 85mmHg, blood gas variables and the risk of post-CA epileptiform EEG activity. The presence of epileptiform activity decreased the likelihood of survival independently (OR: 0.10, 95% CI: 0.04-0.24). Interestingly, survival rates of patients in whom the epileptiform EEG resolved (n=20), were similar compared to patients without epileptiform activity on EEG (60% vs 67%,p=0.617). Other independent predictors of survival were presence of basic life support (BLS) (OR:5.08, 95% CI 1.98-13.98), presence of a shockable rhythm (OR: 7.03, 95% CI: 3.18-16.55), average PaO2 (OR=0.93, CI 95% 0.90-0.96) and% time MAP<65mmHg (OR: 0.96, CI 95% 0.94-0.98). CONCLUSION: Epileptiform EEG activity in post-CA patients is independently and inversely associated with survival and this effect is mainly driven by patients in whom this pattern is refractory over time despite treatment with anti-epileptic drugs. We did not identify an association between hemodynamic factors, blood gas variables and epileptiform EEG activity after CA, although both hypotension, hypoxia and epileptic EEG activity were predictors of survival.

Low hemoglobin levels are associated with lower cerebral saturations and poor outcome after cardiac arrest.

PURPOSE: Post-cardiac arrest (CA) patients have a large cerebral penumbra at risk for secondary ischemic damage in case of suboptimal brain oxygenation during ICU stay. The aims of this study were to investigate the association between hemoglobin, cerebral oxygenation (SctO2) and outcome in post-CA patients. METHODS: Prospective observational study in 82 post-CA patients. Hemoglobin, a corresponding SctO2 measured by NIRS and SVO2 in patients with a pulmonary artery catheter (n=62) were determined hourly during hypothermia in the first 24h of ICU stay. RESULTS: We found a strong linear relationship between hemoglobin and mean SctO2 (SctO2=0.70×hemoglobin+56 (R(2) 0.84, p=10(-6))). Hemoglobin levels below 10g/dl generally resulted in lower brain oxygenation. There was a significant association between good neurological outcome (43/82 patients in CPC 1-2 at 180 days post-CA) and admission hemoglobin above 13g/dl (OR 2.76, 95% CI 1.09:7.00, p=0.03) or mean hemoglobin above 12.3g/dl (OR 2.88, 95%CI 1.02:8.16, p=0.04). This association was entirely driven by results obtained in patients with a mean SVO2 below 70% (OR 6.25, 95%CI 1.33:29.43, p=0.01) and a mean SctO2 below 62.5% (OR 5.87, 95%CI 1.08:32.00, p=0.03). CONCLUSION: Hemoglobin levels below 10g/dl generally resulted in lower cerebral oxygenation. Average hemoglobin levels below 12.3g/dl were associated with worse outcome in patients with suboptimal SVO2 or SctO2. The safety of a universal restrictive transfusion threshold of 7g/dl can be questioned in post-CA patients.

Hemodynamic targets during therapeutic hypothermia after cardiac arrest: A prospective observational study.

AIM: In analogy with sepsis, current post-cardiac arrest (CA) guidelines recommend to target mean arterial pressure (MAP) above 65 mmHg and SVO2 above 70%. This is unsupported by mortality or cerebral perfusion data. The aim of this study was to explore the associations between MAP, SVO2, cerebral oxygenation and survival. METHODS: Prospective, observational study during therapeutic hypothermia (24h - 33 °C) in 82 post-CA patients monitored with near-infrared spectroscopy. RESULTS: Forty-three patients (52%) survived in CPC 1-2 until 180 days post-CA. The mean MAP range associated with maximal survival was 76-86 mmHg (OR 2.63, 95%CI [1.01; 6.88], p = 0.04). The mean SVO2 range associated with maximal survival was 67-72% (OR 8.23, 95%CI [2.07; 32.68], p = 0.001). In two separate multivariate models, a mean MAP (OR 3.72, 95% CI [1.11; 12.50], p=0.03) and a mean SVO2 (OR 10.32, 95% CI [2.03; 52.60], p = 0.001) in the optimal range persisted as independently associated with increased survival. Based on more than 1625000 data points, we found a strong linear relation between SVO2 (range 40-90%) and average cerebral saturation (R(2) 0.86) and between MAP and average cerebral saturation for MAP's between 45 and 101 mmHg (R(2) 0.83). Based on our hemodynamic model, the MAP and SVO2 ranges associated with optimal cerebral oxygenation were determined to be 87-101 mmHg and 70-75%. CONCLUSION: we showed that a MAP range between 76-86 mmHg and SVO2 range between 67% and 72% were associated with maximal survival. Optimal cerebral saturation was achieved with a MAP between 87-101 mmHg and a SVO2 between 70% and 75%. Prospective interventional studies are needed to investigate whether forcing MAP and SVO2 in the suggested range with additional pharmacological support would improve outcome.

Accuracy of continuous thermodilution cardiac output monitoring by pulmonary artery catheter during therapeutic hypothermia in post-cardiac arrest patients.

PURPOSE: Thermodilution continuous cardiac output measurements (TDCCO) by pulmonary artery catheter (PAC) have not been validated during therapeutic hypothermia in post-cardiac arrest patients. The calculated cardiac output based on the indirect Fick principle (FCO) using pulmonary artery blood gas mixed venous oxygen saturation (FCO-BG-SvO2) is considered as the gold standard. Continuous SvO2 by PAC (PAC-SvO2) has also not been validated previously during hypothermia. The aims of this study were (1) to compare FCO-BG-SvO2 with TDCCO, (2) to compare PAC-SvO2 with BG-SvO2 and finally (3) to compare FCO with SvO2 obtained via PAC or blood gas. METHODS: We analyzed 102 paired TDCCO/FCO-BG-SvO2 and 88 paired BG-SvO2/PAC-SvO2 measurements in 32 post-cardiac arrest patients during therapeutic hypothermia. RESULTS: TDCCO was significantly although poorly correlated with FCO-BG-SvO2 (R2 0.21, p<0.01) without systematic bias (-0.15±1.76 l/min). Analysis according to Bland and Altman however showed broad limits of agreement ([-3.61; 3.45] l/min) and an unacceptable high percentage error (105%). None of the criteria for clinical interchangeability were met. Concordance analysis showed that TDCCO had limited trending ability (R2 0.03). FCO based on PAC-SvO2 was highly correlated with FCO-BG-SvO2 (R2 0.72) with a small bias (-0.08±0.72 l/min) and slightly too high percentage error (44%). CONCLUSION: Our results show an extreme inaccuracy of TDCCO by PAC in post-cardiac arrest patients during therapeutic hypothermia. We found a reasonable correlation between BG-SvO2 and PAC-SvO2 and subsequently between FCO calculated with SvO2 obtained either via blood gas or PAC. The decision to start or titrate inotropics should therefore not be guided by TDCCO in this setting.

[Newer inhalation anaesthetics and neuro-anaesthesia: what is the place for sevoflurane or desflurane?]. / Les nouveaux agents volatils halogénés en neuro-anesthésie: quelle place pour le sévoflurane ou le desflurane?

The effects on cerebral circulation and metabolism of sevoflurane and desflurane are largely comparable to isoflurane. Both induce a direct vasodilation of the cerebral vessels, resulting in a less pronounced decrease in cerebral blood flow compared to the decrease in cerebral metabolism. This direct vasodilation seems to be dose-dependent and more pronounced for desflurane > isoflurane > sevoflurane. Many reports suggest luxury perfusion at high concentrations of desflurane. Sevoflurane maintains intact cerebral autoregulation up to 1.5 MAC. Desflurane induces a significant impairment in autoregulation, with a completely abolished autoregulation at 1.5 MAC. Both sevoflurane and desflurane (up to 1.5 MAC) maintain normal CO(2) regulation. As to their effect on final intracranial pressure (ICP), both sevoflurane and desflurane revealed no increases in ICP. However, compared to intravenous hypnotics, subdural ICP is higher with volatiles because of their tendency to increase cerebral swelling after dura opening (isoflurane > sevoflurane). Several case reports have noted seizure-like movements, as well as EEG recorded seizures during induction of sevoflurane anesthesia. Especially, in children during inhalational induction with hyperventilation at a high sevoflurane concentration, severe epileptiform EEG with a hyperdynamic response were observed, which urges for caution using inhalational sevoflurane induction in children for neurosurgical procedures. Neuroprotective properties (reduced neuronal death either by necrosis or apoptosis) have been attributed to all volatile agents. However, these neuroprotective effects have been described in experimental or animal models, so their possible effect on humans remains to be proven.

The acute care of traumatic brain injury.

During the past few decades, management of acute traumatic brain injury has advanced substantially on several fronts. Implementation of rapid transport systems and the advent of trauma centres, together with advances in emergency medicine, critical care medicine and trauma neurosurgery, have improved outcome following head injury. Technological advances made during the past years in the field of invasive neuromonitoring that provide real-time information on brain oxygenation may further improve outcome by enabling individualized therapies for intracranial hypertension. Furthermore, these recent technological advances will provide insights into the pathophysiological processes that are active in traumatic brain injury and a better understanding of the biochemical effects of specific therapeutic regimens.

Influence of intravenous clonidine pretreatment on anesthetic requirements during bispectral EEG-guided sevoflurane anesthesia.

STUDY OBJECTIVE: To assess the anesthetic effects of clonidine during sevoflurane anesthesia guided by the bispectral index (BIS), which is a processed EEG variable correlated with anesthetic-hypnotic depth. DESIGN: Placebo-controlled, double-blind clinical trial. SETTINGS: Elective laparoscopic surgery. PATIENTS: 60 ASA physical status I patients scheduled for laparoscopic surgery. INTERVENTIONS: Patients received either clonidine (3 micrograms/kg, 15 min before induction) or placebo premedication for a sevoflurane-induced and sevoflurane-maintained anesthesia. Sevoflurane was titrated against a BIS held between 40 and 50. Analgesia was provided by local infiltration with bupivacaine. Need for postoperative analgesia was recorded. RESULTS AND CONCLUSION: Mean sevoflurane requirements were not lower with clonidine pretreatment. There was statistically better perioperative hemodynamic stability (i.e., fewer episodes of hypertension and tachycardia) without clinical relevance. A decreased need for postoperative analgesia was observed.

New developments in cerebral monitoring.

In past years, cerebral monitoring was mostly focused around global cerebral perfusion and metabolism monitoring, with the use of transcranial Doppler recordings, jugular bulb oximetry and near-infrared spectroscopy. Most of the recently introduced cerebral monitoring modalities, such as brain tissue partial oxygen tension monitoring and cerebral microdialysis, offer new opportunities by providing regional information on the specific brain area in which the probe is inserted. Ideally, these probes should be inserted in that area of the brain that is most vulnerable to ischaemia, but that may be salvageable with appropriate therapy. In this case, the combination of global and regional cerebral monitoring might offer the best information on which to base patient management. Also, the introduction of more clinically useful, functional neuroimaging techniques may be a valuable adjunct to future neurological critical care management.

[Early enteral feeding in cranial trauma]. / L'alimentation entérale précoce du traumatisé crânien.

Until some years ago, patients suffering from head injury were poorly fed and nutrition was not a primary concern in the medical treatment of these patients. To date, six studies on head-injury patients have examined the effect of nutritional support on their outcome. All showed that lack of adequate nutrition contributed to increased mortality and morbidity. Head-injured patients on conventional enteral nutrition receive significantly less calories and proteins, resulting in an increased morbidity and mortality rate. Most of the severely head injured patients receiving enteral nutrition do not tolerate enteral feedings because of abnormal gastric emptying. The mechanisms of altered gastric function remain obscure. Increased intracranial pressure, cytokines, corticotropin-releasing factor, opiates, and other agents may all play a role. Impaired gastric motility has led to increasing use of small bowel feeding in head-injured patients. Jejunal feeding enables a higher caloric input and a better nitrogen balance. Moreover, it enables early enteral administration of nutrients in a safe and efficient way. Early administration of nutrients may be extremely important as it seems to decrease the hypermetabolic response to traumatic injury. Therefore, early jejunal enteral feeding may become an important cornerstone in the medical management of head-injured patients.

Comparison of spontaneous frontal EMG, EEG power spectrum and bispectral index to monitor propofol drug effect and emergence.

BACKGROUND: The aim of this study was to investigate the accuracy of frontal spontaneous electromyography (SEMG) and EEG spectral edge frequency (SEF 95%), median frequency (MF), relative delta power (RDELTA) and bispectral index (BIS) in monitoring loss of and return of consciousness and hypnotic drug effect during propofol administration at different calculated plasma target concentrations. METHODS: Propofol was administered by using a target-controlled infusion at different propofol steady-state concentrations. All variables were measured simultaneously at specific calculated concentrations and endpoints. RESULTS: Loss of consciousness was accurately monitored by BIS, SEMG and SEF 95%, and propofol drug effect by BIS only. Return of consciousness was predicted by BIS, MF and SEF 95%. Due to the biphasic EEG pattern of propofol and the lack of reproducible data at specific propofol concentrations, the clinical usefulness of SEF 95%, MF and RDELTA was very limited. SEMG was useful to detect loss and return of consciousness, but without predictive value. CONCLUSIONS: The BIS might be an accurate measure to monitor depth of anaesthesia and hypnotic drug effect. Other neurophysiologic measures have limited value to monitor depth of anaesthesia and hypnotic drug effect.

Subjective complaints versus neuropsychological test performance after moderate to severe head injury.

Neuropsychological test performance and subjective complaints of 85 patients with moderate to severe head injury were investigated at 6 months postinjury. The neuropsychological test battery included 10 measures of attention, memory, mental flexibility, reaction time, visuoconstruction and verbal fluency. Subjective complaints were assessed using a self-report questionnaire subdivided into four subscales (somatic, cognitive, emotional and behavioural). Ratings were obtained for the pre-injury and current status. Thirty-three trauma patients with injuries to other parts of the body than the head were used as controls. For the head injured, relatives also completed the questionnaire. Head injured patients performed significantly below trauma control patients on nearly all test measures. Head injured patients and their relatives reported a significant increase in subjective complaints since the injury on all four subscales, with no differences between patients' and relatives' reports. These changes were also reported by the trauma controls, but they report fewer changes in somatic and cognitive functioning. Exploratory canonical correlation analyses revealed no correlations between any of the four scales of the questionnaire and the test measures, nor for the head injured, the trauma controls, or the relatives, indicating no relevant relationship between subjective complaints and neuropsychological test performance.

Jugular bulb oximetry: review on a cerebral monitoring technique.

Jugular bulb oximetry is the first available continuous monitoring method estimating the adequacy of cerebral perfusion. Despite its major technical as well as methodological shortcomings the information on the oxygen supply to demand balance of the brain seems most valuable. Especially the deleterious consequences of systemic variations (mainly concerning arterial blood pressure and CO2-tension) on the diseased brain are revealed by jugular bulb saturation values. The prevention and/or the early detection of these systemic secondary insults could have important implications as to final neurological outcome. Jugular bulb oximetry could also guide specific intracranial antihypertensive treatment, as it may reveal the pathophysiological mechanisms behind intracranial hypertension with regard to the status of cerebral perfusion (cerebral hyperemia or cerebral hypoperfusion). These insights might increase the efficacy of all treatments available for intracranial hypertension.

Cerebral perfusion pressure and intracranial pressure in relation to neuropsychological outcome.

OBJECTIVE: The study attempted to examine the relationship between neuropsychological functioning and reduced cerebral perfusion pressure (CPP), raised intracranial pressure (ICP), and reduced mean arterial pressure (MAP), monitored during intensive care treatment. DESIGN: This prospective follow-up study included consecutive patients and evaluated outcome at 6 months postinjury by the administration of a neuropsychological test battery. SETTING: The study was conducted at the University Hospital of Gent, Belgium. PATIENTS AND PARTICIPANTS: Over a 30-month period, 43 patients were included. Inclusion criteria were the following: hospital admission following closed head injury. ICP monitoring, no medical history of central nervous system disease or mental retardation, survival for at least 6 months, and informed consent for participation. INTERVENTIONS: All patients received the hospital's standard treatment for head injury, which remained unchanged during the study period. MEASUREMENTS AND RESULTS: Reduced CPP was analyzed using the number of observed values below 70 mmhg, raised ICP using the number of values above 20 mmHg, and MAP using the number of values below 80 mmHg. The neuropsychological test battery included 11 measures of attention, information processing, motor reaction time, memory, learning, visuoconstruction, verbal fluency, and mental flexibility. No linear relationships were found between overall neuropsychological impairment and episodes of reduced CPP, raised ICP, or reduced MAP. CONCLUSIONS: Although reduced CPP and raised ICP are frequent, often fatal, complications of head injury, in survivors they do not seem to be related to later neuropsychological functioning.

Use of continuous bispectral EEG monitoring to assess depth of sedation in ICU patients.

Monitoring the depth of sedation in patients under intensive care is difficult. Clinical assessment by the different scoring systems produces insufficient information, especially once deeply sedated patients become unresponsive to any external stimulation. Recently, the bispectral index (BIS), the result of computerized bispectral electroencephalographic monitoring, was found to be the best predictor of depth of anaesthesia during surgical intervention. This report concerns BIS monitoring in 18 randomly selected, deeply sedated, surgical patients in the intensive care unit, who were unresponsive to standard clinical stimulation (Ramsay sedation score). A wide range of BIS was observed, with 15 of the patients having a BIS below 60, indicating a state of deep sedation (or possibly over-sedation). Therefore, further studies using BIS monitoring in patients under intensive care are needed to determine if this method can guide sedation and prevent oversedation in this context and, most importantly, to analyse its final cost-benefit ratio.

Personality change following head injury: assessment with the NEO Five-Factor Inventory.

We evaluated personality change following head injury in 68 patients at 6 months postinjury using the NEO Five-Factor Inventory to assess the five personality dimensions of the Five-Factor Model of Personality. All items had to be rated twice, once for the preinjury and once for the current status. Twenty-eight trauma patients with injuries to other parts of the body than the head were used as controls. For the head-injured group, 63 relatives also completed the questionnaire. The results showed no differences between the ratings of head-injured patients and the ratings of trauma control patients. Both groups showed significant change in the personality dimensions Neuroticism, Extraversion, and Conscientiousness. Compared to their relatives, head-injured patients report a smaller change in Extraversion and Conscientiousness. Changes were not reported on the Openness and Agreeableness scales, by neither the head-injured or their relatives, nor by the trauma controls.

Analysis of very early jugular bulb oximetry data after severe head injury: implications for the emergency management?

Jugular bulb oximetry provides the first bedside available information on cerebral oxygen utilization. An extensive analysis was made of all initial jugular bulb oximetry data obtained in 150 patients within the first 12 h after severe traumatic brain injury. These data revealed initial abnormal jugular bulb saturation values in 57 patients (= 38% of study population), with a predominance of jugular bulb desaturation (observed in 45 patients). This confirms earlier reports that revealed a high incidence of disturbed and inadequate cerebral perfusion in the first hours after brain injury. Jugular bulb desaturation was especially related to systemic causes (such as a lowered cerebral perfusion pressure observed in 29 patients, and a lowered arterial carbon dioxide tension in 24 patients). These findings could have important implications for the emergency management of severely head-injured patients, as outcome might possibly be improved by better attention to all systemic factors that might reduce cerebral perfusion in the early hours after traumatic insult.